The Role of Dioxin Receptor in Mammary Development and Carcinogenesis
Abstract
The aromatic hydrocarbon (or dioxin) receptor (AhR) which is a ligand-activated basic helix-loop-helix (bHLH) transcription factor, mediates the toxic responses of dioxin. The research in this proposal is testing the hypothesis that the dioxin receptor (AhR) plays a central role in regulating the mammary epithelial network during the gland development, as well as regulating major events in mammary carcinogenesis. Following on preliminary observation of the dramatic up-regulation of this receptor in advanced human breast carcinoma (HBC) cell lines, we proposed to address the question of whether the AhR overexpression alone is sufficient for transforming normal mammary epithelia, and whether it is causally associated transformation, using two genetic approaches. The AhR expression will be blocked in high tumorigenic HBC cell lines by siRNA technology to demonstrate a direct role of the AhR in modifying the progression of metastasis. To directly address the effect of increased expression of AhR, the human AhR cDNA will be stably transfected and over-expressed in a normal mammary epithelia and in non-tumorigenic human breast cell line. The development of metastatic phenotypes in the AhR-transformed lines will be assayed as their ability for anchorage-independent growth in soft agar media and for inducing tumors in nude mouse.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA430251
Entities
People
- Sakina E. Eltom
Organizations
- Meharry Medical College